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Natural History of Rising Serum Prostate-Specific Antigen in Men With Castrate Nonmetastatic Prostate Cancer

From the Massachusetts General Hospital, Boston, MA; University of California at Los Angeles, Los Angeles; University of California at San Francisco, San Francisco; Western Clinical Research, Torrance, CA; University of Montreal, Montreal, Canada; University of Maryland, Baltimore, MD; S Florida Medical Research, Aventura, FL; Christchurch Hospital, Christchurch, New Zealand; Peter MacCallum Cancer Institute, Melbourne, Australia; Free University of Brussels, Brussels, Belgium; Novartis Oncology, East Hanover, NJ; University of Waterloo, Waterloo, Canada; and University of Washington, Seattle, WA

Address reprint requests to Matthew R. Smith, MD, PhD, Massachusetts General Hospital, Cox 640, 100 Blossom St, Boston, MA 02114; e-mail: smith.matthew{at}mgh.harvard.edu

PURPOSE: To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy.

PATIENTS AND METHODS:: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity.

RESULTS: At 2 years, 33% of patients had developed bone metastases. Median bone metastasis–free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes.

CONCLUSION: Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.

Supported by Novartis Oncology. M.R.S. is supported by the John and Claire Bertucci Center for Genitourinary Malignancies at Massachusetts General Hospital.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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